NSCLC, Non-Small Cell Lung Carcinoma

NSCLC,非小细胞肺癌
  • 文章类型: Journal Article
    急性肺损伤(ALI)是临床上严重的肺部疾病,发病率和死亡率都很高。尤其是,2019年冠状病毒病(COVID-19)对全球政府健康构成严重威胁。它几乎分布在宇宙的各个角落,COVID-19防控形势依然严峻。中医药在疾病的预防和治疗中起着至关重要的作用。目前,缺乏治疗这些疾病的药物,因此有必要开发治疗COVID-19相关ALI的药物。苦参(D.Don)Hara是of科的一年生植物,也是中国历史悠久的传统医学之一。近年来,其根茎(药用部位)因其显著的抗炎作用而受到国内外学者的关注,抗菌和抗癌活性。它可以在SARS-COV-2上使用多种成分,目标,和路径,并对冠状病毒病2019(COVID-19)相关急性肺损伤(ALI)有一定影响。然而,对其地上部分(包括茎和叶)的系统研究很少,其潜在的治疗机制尚未研究。使用TCMSP数据库收集了F.dibotrys根茎的植物化学成分。并通过代谢组学检测了F.dibotrys的地上部分的代谢产物。通过PharmMapper网站工具预测了F.dibotrys的植物化学目标。从GeneCards中检索到COVID-19和ALI相关基因。通过metscape生物信息学工具,通过基因本体论(GO)和KEGG富集了F.dibotrys中COVID-19和ALI相关基因的交叉靶标和活性植物化学物质。使用Cytoscape软件建立并分解了相互作用的网络进入活性植物化学物质和抗COVID-19和ALI靶标。DiscoveryStudio(2019版)用于对具有抗COVID-19和ALI靶标的关键活性植物化学物质进行分子对接。我们从F.dibotrys的地上部分鉴定出1136种化学物质,其中活性类黄酮和酚类化学物质47种。从F.dibotrys的根茎中搜索到了总共61种化学物质,其中15种是活性化学物质。因此,在F.dibotrys的地上部分和根茎上有6种常见的关键活性化学物质,89这些植物化学物质的潜在目标,和211个COVID-19和ALI相关基因。GO富集表明F.dibotrys可能参与影响包含许多生物学过程的基因靶标,例如,巨核细胞分化的负调控,调节DNA代谢过程,这可以归结为其抗COVID-19相关的ALI效应。KEGG通路表明病毒致癌作用,剪接体,沙门氏菌感染,冠状病毒病-COVID-19,军团菌病和人类免疫缺陷病毒1感染途径是困扰F.dibotrys抗COVID-19相关ALI作用的主要途径。分子对接证实了F.dibotrys的6种关键活性植物化学物质,如木犀草素,(+)-表儿茶素,槲皮素,异鼠李素,(+)-儿茶素,和(-)-儿茶素没食子酸酯,可以与内核治疗靶点NEDD8、SRPK1、DCUN1D1和PARP1结合。体外活性实验表明,在一定范围内,随着浓度的增加,二博特草生部分和根茎的总抗氧化能力增加。此外,作为一个整体,黄曲霉地上部分的抗氧化能力强于根茎。我们的研究为进一步探索F.dibotrys的抗COVID-19相关ALI化学成分和机制提供了线索,并为开发基于F.dibotrys植物化学物质的现代抗COVID-19相关ALI药物提供了科学依据。我们还充分开发了F.dibotrys的地上部分的药用价值,能有效避免资源的浪费。同时,我们的工作为整合代谢组学提供了新的策略,网络药理学,和分子对接技术是识别对中药药理作用有效的有效成分和机制的有效途径。
    Acute lung injury (ALI) is a clinically severe lung illness with high incidence rate and mortality. Especially, coronavirus disease 2019 (COVID-19) poses a serious threat to world wide governmental fitness. It has distributed to almost from corner to corner of the universe, and the situation in the prevention and control of COVID-19 remains grave. Traditional Chinese medicine plays a vital role in the precaution and therapy of sicknesses. At present, there is a lack of drugs for treating these diseases, so it is necessary to develop drugs for treating COVID-19 related ALI. Fagopyrum dibotrys (D. Don) Hara is an annual plant of the Polygonaceae family and one of the long-history used traditional medicine in China. In recent years, its rhizomes (medicinal parts) have attracted the attention of scholars at home and abroad due to their significant anti-inflammatory, antibacterial and anticancer activities. It can work on SARS-COV-2 with numerous components, targets, and pathways, and has a certain effect on coronavirus disease 2019 (COVID-19) related acute lung injury (ALI). However, there are few systematic studies on its aerial parts (including stems and leaves) and its potential therapeutic mechanism has not been studied. The phytochemical constituents of rhizome of F. dibotrys were collected using TCMSP database. And metabolites of F. dibotrys\' s aerial parts were detected by metabonomics. The phytochemical targets of F. dibotrys were predicted by the PharmMapper website tool. COVID-19 and ALI-related genes were retrieved from GeneCards. Cross targets and active phytochemicals of COVID-19 and ALI related genes in F. dibotrys were enriched by gene ontology (GO) and KEGG by metscape bioinformatics tools. The interplay network entre active phytochemicals and anti COVID-19 and ALI targets was established and broke down using Cytoscape software. Discovery Studio (version 2019) was used to perform molecular docking of crux active plant chemicals with anti COVID-19 and ALI targets. We identified 1136 chemicals from the aerial parts of F. dibotrys, among which 47 were active flavonoids and phenolic chemicals. A total of 61 chemicals were searched from the rhizome of F. dibotrys, and 15 of them were active chemicals. So there are 6 commonly key active chemicals at the aerial parts and the rhizome of F. dibotrys, 89 these phytochemicals\'s potential targets, and 211 COVID-19 and ALI related genes. GO enrichment bespoken that F. dibotrys might be involved in influencing gene targets contained numerous biological processes, for instance, negative regulation of megakaryocyte differentiation, regulation of DNA metabolic process, which could be put down to its anti COVID-19 associated ALI effects. KEGG pathway indicated that viral carcinogenesis, spliceosome, salmonella infection, coronavirus disease - COVID-19, legionellosis and human immunodeficiency virus 1 infection pathway are the primary pathways obsessed in the anti COVID-19 associated ALI effects of F. dibotrys. Molecular docking confirmed that the 6 critical active phytochemicals of F. dibotrys, such as luteolin, (+) -epicatechin, quercetin, isorhamnetin, (+) -catechin, and (-) -catechin gallate, can combine with kernel therapeutic targets NEDD8, SRPK1, DCUN1D1, and PARP1. In vitro activity experiments showed that the total antioxidant capacity of the aerial parts and rhizomes of F. dibotrys increased with the increase of concentration in a certain range. In addition, as a whole, the antioxidant capacity of the aerial part of F. dibotrys was stronger than that of the rhizome. Our research afford cues for farther exploration of the anti COVID-19 associated ALI chemical compositions and mechanisms of F. dibotrys and afford scientific foundation for progressing modern anti COVID-19 associated ALI drugs based on phytochemicals in F. dibotrys. We also fully developed the medicinal value of F. dibotrys\' s aerial parts, which can effectively avoid the waste of resources. Meanwhile, our work provides a new strategy for integrating metabonomics, network pharmacology, and molecular docking techniques which was an efficient way for recognizing effective constituents and mechanisms valid to the pharmacologic actions of traditional Chinese medicine.
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  • 文章类型: Case Reports
    未经证实:我们报告了一例罕见的患者,包块累及肺门和心脏,但其具体性质无法确定。术后病理证实SCLC。这表明,根治性手术切除T4SCLC应被视为多模式治疗的重要组成部分。
    未经证实:一位49岁的绅士抱怨有一个星期的轻微胸闷。在CECT上在左心房和左肺门检测到两个大肿块病变。在MDT讨论之后,建议扩大切除范围.术后病理为完整切除,无残留,淋巴结阴性。
    未经证实:由于肺转移到心脏的罕见,确定肺门质量和心脏质量之间的同源性至关重要。基于此,同时进行手术治疗,消除这些危害对患者非常有益,比如急性机械性心脏阻塞,和心脏栓塞.我们的文献综述表明,SCLC肿瘤在心脏转移后进展迅速,限制了完全切除的机会.此外,NSCLC中T4肿瘤的完全切除已经尝试了很多次,所以它也应该在SCLC上尝试。
    未经证实:SCLC肿瘤一旦植入心脏就会迅速进展。激进的手术,如根治性切除术可以减少肿瘤负担,将急性猝死的风险降至最低,并改善患者的后续治疗,所有这些都可能延长患者的生存期。
    UNASSIGNED: We report a rare case of a patient with a mass involving both the hilum and the heart, but its specific nature could not be determined. SCLC was confirmed by postoperative pathology. It revealed that radical surgical resection for T4 SCLC should be considered an important part of multimodality treatment.
    UNASSIGNED: A 49-year-old gentleman complained of mild chest tightness for a week. Two large mass lesions were detected on CECT in the left atrium and left hilum. After an MDT discussion, an extended resection was recommended. Postoperative pathology denoted a complete excision with no residuals and negative lymph nodes.
    UNASSIGNED: Due to the rarity of lung metastases to the heart, it is vital to determine the homology between the hilar mass and the cardiac mass. Based on this, simultaneous surgical treatment is done and it is very beneficial for patients by eliminating those hazards, such as acute mechanical cardiac obstruction, and cardiac embolism. Our literature review demonstrates that the SCLC tumour progresses rapidly after cardiac metastasis, limiting the chance of a complete resection. Furthermore, complete resection of T4 tumours in NSCLC has been attempted many times, so it should also be tried on SCLC.
    UNASSIGNED: It is common for SCLC tumours to progress rapidly once they havemetastasized to the heart. An aggressive operation such as radical resection can reduce tumor burdens, minimize the risk of sudden acute death and improve patient follow-up treatment, all of which may prolong the survival of patients.
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  • 文章类型: Journal Article
    目的:本研究旨在确定非小细胞肺癌患者的特定临床和计算机断层扫描(CT)模式的存在是否与表皮生长因子受体(EGFR)突变有关。
    方法:在2002年1月至2021年7月之间在6个数据库中进行了系统的文献综述和荟萃分析。使用比值比(OR)测量并合并临床和CT模式以检测EGFR突变之间的关系。这些结果用于建立几个数学模型来预测EGFR突变。
    结果:34项回顾性诊断准确性研究符合纳入和排除标准。结果表明,毛玻璃不透明度(GGO)的OR为1.86(95CI1.34-2.57),空气支气管造影OR1.60(95CI1.38-1.85),血管会聚OR1.39(95CI1.12-1.74),胸膜回缩OR1.99(95CI1.72-2.31),刺突或1.42(95CI1.19-1.70),空化或0.70(95CI0.57-0.86),早期疾病阶段OR1.58(95CI1.14-2.18),非吸烟者状态或2.79(95CI2.34-3.31),女性OR2.33(95CI1.97-2.75)。建立了数学模型,包括评估的所有临床和CT模式,曲线下面积(AUC)为0.81。
    结论:GGO,空气支气管图,血管会聚,胸膜回缩,针状边缘,疾病早期阶段,女性性别,和非吸烟状态是EGFR突变的重要危险因素。同时,空化是EGFR突变的保护因素。建立的数学模型可以很好地预测肺腺癌患者的EGFR突变。
    OBJECTIVE: This study aims to determine if the presence of specific clinical and computed tomography (CT) patterns are associated with epidermal growth factor receptor (EGFR) mutation in patients with non-small cell lung cancer.
    METHODS: A systematic literature review and meta-analysis was carried out in 6 databases between January 2002 and July 2021. The relationship between clinical and CT patterns to detect EGFR mutation was measured and pooled using odds ratios (OR). These results were used to build several mathematical models to predict EGFR mutation.
    RESULTS: 34 retrospective diagnostic accuracy studies met the inclusion and exclusion criteria. The results showed that ground-glass opacities (GGO) have an OR of 1.86 (95%CI 1.34 -2.57), air bronchogram OR 1.60 (95%CI 1.38 - 1.85), vascular convergence OR 1.39 (95%CI 1.12 - 1.74), pleural retraction OR 1.99 (95%CI 1.72 - 2.31), spiculation OR 1.42 (95%CI 1.19 - 1.70), cavitation OR 0.70 (95%CI 0.57 - 0.86), early disease stage OR 1.58 (95%CI 1.14 - 2.18), non-smoker status OR 2.79 (95%CI 2.34 - 3.31), female gender OR 2.33 (95%CI 1.97 - 2.75). A mathematical model was built, including all clinical and CT patterns assessed, showing an area under the curve (AUC) of 0.81.
    CONCLUSIONS: GGO, air bronchogram, vascular convergence, pleural retraction, spiculated margins, early disease stage, female gender, and non-smoking status are significant risk factors for EGFR mutation. At the same time, cavitation is a protective factor for EGFR mutation. The mathematical model built acts as a good predictor for EGFR mutation in patients with lung adenocarcinoma.
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  • 文章类型: Journal Article
    OBJECTIVE: Explore the longitudinal CT-based radiomics to demonstrate the changing trend of radiotherapy response and to determine at which point after the onset of treatment radiomics exhibit the greatest change for stage III NSCLC patients.
    METHODS: Ten stage III NSCLC patients in line with inclusion criteria were enrolled retrospectively, each of whom received radiotherapy or concurrent chemo-radiotherapy and performed eight series of follow-up CT imaging. Longitudinal radiomics were extracted on region of interest from the eight registered images, then two steps were conducted to select significant features as indicators of tumor change: 1) stable features were selected by Kendall rank correlation; 2) texture feature types with a steadily changing trend were retained and intensity features with stable change trends were selected to represent the large number of them. Next, the trend and rate of tumor change were analyzed using the Delta method and Curve-fitting method. Finally, the statistics in the distribution of stable features in patients were calculated.
    RESULTS: 675 stable features were selected from a total number of 1371 radiomics features, then 12 texture features types were retained and three intensity features were chosen to represent their own category. Among the final selected feature types, it was found that the two time points were weeks 1 and 3 with the higher rate of change. One patient had very few stable tumor features out of a total of 101 features, and the rate of change of features of another patient was conspicuously higher than the average level with number of 301 features.
    CONCLUSIONS: The longitudinal CT radiomics could demonstrate the change trend of tumor and at which point exhibit the greatest change during radiotherapy, and potentially be used for treatment decisions concerning adaptive radiotherapy.
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  • 文章类型: Journal Article
    2019年冠状病毒病(COVID-19)的爆发是由新出现的冠状病毒(2019-nCoV别名SARS-CoV-2)引起的,类似于严重急性呼吸道综合症病毒(SARS-CoV)。首次在武汉(中国)发现的SARS-CoV-2已在全球传播,导致全球范围内的高死亡率,迄今为止约有400万人死亡。截至2021年7月第一周,已报告约1.81亿例COVID-19病例。SARS-CoV-2感染是由病毒刺突蛋白与血管紧张素转换酶2(ACE2)的结合介导的。ACE2在许多人体组织中表达;然而,主要的切入点可能是肺细胞,负责肺中肺泡表面活性剂的合成。肺细胞的病毒感染会损害免疫反应并导致,除了气体交换导致的严重缺氧,有严重并发症的疾病。在病毒感染期间,介导病毒进入的基因产物(例如ACE2),抗原呈递,细胞免疫至关重要。人类白细胞抗原(HLA)I和II向CD8和CD4T淋巴细胞呈递抗原,这对于抵抗包括病毒在内的病原体的免疫防御至关重要。HLA基因变体影响病毒抗原肽对T细胞的识别和呈递,和细胞因子分泌。此外,内质网氨肽酶(ERAP)修剪抗原前体肽以适应MHCI类分子的结合槽。导致ERAP异常的ERAP基因多态性可改变HLAI类分子的抗原呈递,从而导致异常的T细胞应答,这可能会影响对感染的易感性和/或免疫反应的激活。这些基因的多态性是相关的,在全球遗传关联研究中,具有各种表型特征/疾病,其中许多与COVID-19的发病机理和进展有关;基因型组织表达数据中注释了来自各种基因的多态性,它们调节ACE2,HLA\和ERAP\的表达。我们回顾了这种多态性,并说明了其等位基因频率在全球人群中的变化。这些报道的发现强调了遗传调节剂(例如,ACE2,HLA和ERAP的基因型变化导致表达基因产物的异常或调节这些基因表达水平的其他基因的基因型变化)在发病机制中的作用。病毒感染。
    The outbreak of coronavirus disease 2019 (COVID-19) was caused by the newly emerged corona virus (2019-nCoV alias SARS-CoV-2) that resembles the severe acute respiratory syndrome virus (SARS-CoV). SARS-CoV-2, which was first identified in Wuhan (China) has spread globally, resulting in a high mortality worldwide reaching ~4 million deaths to date. As of first week of July 2021, ~181 million cases of COVID-19 have been reported. SARS-CoV-2 infection is mediated by the binding of virus spike protein to Angiotensin Converting Enzyme 2 (ACE2). ACE2 is expressed on many human tissues; however, the major entry point is probably pneumocytes, which are responsible for synthesis of alveolar surfactant in lungs. Viral infection of pneumocytes impairs immune responses and leads to, apart from severe hypoxia resulting from gas exchange, diseases with serious complications. During viral infection, gene products (e.g. ACE2) that mediate viral entry, antigen presentation, and cellular immunity are of crucial importance. Human leukocyte antigens (HLA) I and II present antigens to the CD8+ and CD4+ T lymphocytes, which are crucial for immune defence against pathogens including viruses. HLA gene variants affect the recognition and presentation of viral antigenic peptides to T-cells, and cytokine secretion. Additionally, endoplasmic reticulum aminopeptidases (ERAP) trim antigenic precursor peptides to fit into the binding groove of MHC class I molecules. Polymorphisms in ERAP genes leading to aberrations in ERAP\'s can alter antigen presentation by HLA class I molecules resulting in aberrant T-cell responses, which may affect susceptibility to infection and/or activation of immune response. Polymorphisms from these genes are associated, in global genetic association studies, with various phenotype traits/disorders many of which are related to the pathogenesis and progression of COVID-19; polymorphisms from various genes are annotated in genotype-tissue expression data as regulating the expression of ACE2, HLA\'s and ERAP\'s. We review such polymorphisms and illustrate variations in their allele frequencies in global populations. These reported findings highlight the roles of genetic modulators (e.g. genotype changes in ACE2, HLA\'s and ERAP\'s leading to aberrations in the expressed gene products or genotype changes at other genes regulating the expression levels of these genes) in the pathogenesis of viral infection.
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  • 文章类型: Journal Article
    肝细胞生长因子(HGF)/c-Met途径与胚胎发生和器官发育和分化有关。种系或体细胞突变,染色体重排,基因扩增,MET的转录上调或自分泌或旁分泌c-Met信号的改变与癌细胞增殖和存活有关,包括肾细胞癌(RCC),并与疾病进展有关。已经显示HGF/c-Met途径在具有骨转移(BMs)的肿瘤中特别相关。然而,靶向c-Met在骨转移疾病中的疗效,包括在碾压混凝土中,还没有被证明。因此,需要进一步研究HGF/c-Met通路在骨微环境(BME)中的特殊作用,以及如何在骨转移疾病中有效靶向该通路.
    Hepatocyte growth factor (HGF)/c-Met pathway is implicated in embryogenesis and organ development and differentiation. Germline or somatic mutations, chromosomal rearrangements, gene amplification, and transcriptional upregulation in MET or alterations in autocrine or paracrine c-Met signalling have been associated with cancer cell proliferation and survival, including in renal cell carcinoma (RCC), and associated with disease progression. HGF/c-Met pathway has been shown to be particularly relevant in tumors with bone metastases (BMs). However, the efficacy of targeting c-Met in bone metastatic disease, including in RCC, has not been proven. Therefore, further investigation is required focusing the particular role of HGF/c-Met pathway in bone microenvironment (BME) and how to effectively target this pathway in the context of bone metastatic disease.
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  • 文章类型: Journal Article
    下一代测序(NGS)极大地改善了癌症研究和临床试验的灵活性和结果,为大规模基因组测试提供高度敏感和准确的高通量平台。与全基因组(WGS)或全外显子组测序(WES)相比,靶向基因组测序(TS)专注于一组已知与疾病发病机理和/或临床相关性密切相关的基因或靶标,提供更大的测序深度,降低成本和数据负担。这允许靶向测序以高置信度识别靶向区域中的低频率变体。因此适用于分析低质量和片段化的临床DNA样本。因此,TS已广泛用于临床研究和试验,用于患者分层和靶向疗法的开发。然而,它向常规临床应用的过渡一直很缓慢。许多技术和分析障碍仍然存在,需要在大规模和跨中心实施之前进行讨论和解决。迫切需要黄金标准和最先进的程序和管道来加速这一过渡。在这篇综述中,我们首先介绍了TS是如何在癌症研究中进行的,包括各种目标浓缩平台,目标面板的构建,以及利用TS对临床样本进行分析的选定研究和临床研究。然后,我们为TS数据提供了一个通用的分析工作流程,详细讨论了重要的参数和过滤器,旨在提供TS使用和分析的最佳实践。
    Next Generation Sequencing (NGS) has dramatically improved the flexibility and outcomes of cancer research and clinical trials, providing highly sensitive and accurate high-throughput platforms for large-scale genomic testing. In contrast to whole-genome (WGS) or whole-exome sequencing (WES), targeted genomic sequencing (TS) focuses on a panel of genes or targets known to have strong associations with pathogenesis of disease and/or clinical relevance, offering greater sequencing depth with reduced costs and data burden. This allows targeted sequencing to identify low frequency variants in targeted regions with high confidence, thus suitable for profiling low-quality and fragmented clinical DNA samples. As a result, TS has been widely used in clinical research and trials for patient stratification and the development of targeted therapeutics. However, its transition to routine clinical use has been slow. Many technical and analytical obstacles still remain and need to be discussed and addressed before large-scale and cross-centre implementation. Gold-standard and state-of-the-art procedures and pipelines are urgently needed to accelerate this transition. In this review we first present how TS is conducted in cancer research, including various target enrichment platforms, the construction of target panels, and selected research and clinical studies utilising TS to profile clinical samples. We then present a generalised analytical workflow for TS data discussing important parameters and filters in detail, aiming to provide the best practices of TS usage and analyses.
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  • 文章类型: Journal Article
    骨髓来源的抑制细胞(MDSC)在免疫抑制中起重要作用,并在癌症和慢性炎症等病理条件下积累。它们包括通过多种机制发挥其免疫抑制功能的不成熟骨髓细胞的异质群体。免疫球蛋白样转录物3(ILT3)是一种包含基于酪氨酸的免疫受体抑制基序(ITIM)的受体,可以在抗原呈递细胞上表达,并且是树突状细胞耐受性的重要调节剂。ILT3以膜结合和可溶形式存在,可以与T细胞上尚未鉴定的配体相互作用,从而诱导T细胞无反应性,调节性T细胞,或者T抑制细胞.在这项研究中,我们分析了105例非小细胞肺癌患者和20名健康对照者新鲜分离的外周血单个核细胞(PBMC),首次证明ILT3在MDSCs上表达.我们发现循环MDSCs水平升高与存活率降低相关。依据ILT3细胞表面表达,可以区分多形核(PMN)-MDSCs的ILT3low和ILT3high群体.有趣的是,符合ILT3对树突状细胞的免疫抑制功能,与PMN-MDSC升高和ILT3高比例患者相比,PMN-MDSC升高和ILT3高比例患者的中位生存期较短.未发现ILT3high亚群与其他免疫变量之间的相关性。在MDSC上表达的ILT3可能反映了该细胞群诱导免疫抑制的先前未知的机制,因此可能是免疫干预的有吸引力的靶标。
    Myeloid-derived suppressor cells (MDSCs) play an important role in immune suppression and accumulate under pathologic conditions such as cancer and chronic inflammation. They comprise a heterogeneous population of immature myeloid cells that exert their immunosuppressive function via a variety of mechanisms. Immunoglobulin-like transcript 3 (ILT3) is a receptor containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) that can be expressed on antigen-presenting cells and is an important regulator of dendritic cell tolerance. ILT3 exists in a membrane-bound and a soluble form and can interact with a yet unidentified ligand on T cells and thereby induce T-cell anergy, regulatory T cells, or T suppressor cells. In this study, we analyzed freshly isolated peripheral blood mononuclear cells (PBMCs) of 105 patients with non-small cell lung cancer and 20 healthy controls and demonstrated for the first time that ILT3 is expressed on MDSCs. We show that increased levels of circulating MDSCs correlate with reduced survival. On the basis of ILT3 cell surface expression, an ILT3low and ILT3high population of polymorphonuclear (PMN)-MDSCs could be distinguished. Interestingly, in line with the immunosuppressive function of ILT3 on dendritic cells, patients with an increased proportion of PMN-MDSCs and an increased fraction of the ILT3high subset had a shorter median survival than patients with elevated PMN-MDSC and a smaller ILT3high fraction. No correlation between the ILT3high subset and other immune variables was found. ILT3 expressed on MDSCs might reflect a previously unknown mechanism by which this cell population induces immune suppression and could therefore be an attractive target for immune intervention.
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  • 文章类型: Review
    恶性细胞表达可用于引发抗癌免疫应答的抗原。实现该目标的一种方法在于在适当的佐剂存在下施用肿瘤相关抗原(TAA)或其肽作为重组蛋白。在过去的十年里,肽疫苗已被证明在各种小鼠肿瘤模型中介导抗肿瘤作用,特别是在强效免疫刺激方案的情况下给药。尽管有多重限制,首先,抗癌疫苗通常用作治疗(而不是预防)药物,这种免疫治疗范式已经在临床场景中进行了深入的研究,有希望的结果。目前,实验人员和临床医生都将精力集中在鉴定所谓的肿瘤排斥抗原上,即,TAA可以引发导致疾病根除的免疫反应,以及对患者具有优异辅助活性的联合免疫刺激干预措施。这里,我们总结了用于癌症治疗的肽疫苗开发的最新进展。
    Malignant cells express antigens that can be harnessed to elicit anticancer immune responses. One approach to achieve such goal consists in the administration of tumor-associated antigens (TAAs) or peptides thereof as recombinant proteins in the presence of adequate adjuvants. Throughout the past decade, peptide vaccines have been shown to mediate antineoplastic effects in various murine tumor models, especially when administered in the context of potent immunostimulatory regimens. In spite of multiple limitations, first of all the fact that anticancer vaccines are often employed as therapeutic (rather than prophylactic) agents, this immunotherapeutic paradigm has been intensively investigated in clinical scenarios, with promising results. Currently, both experimentalists and clinicians are focusing their efforts on the identification of so-called tumor rejection antigens, i.e., TAAs that can elicit an immune response leading to disease eradication, as well as to combinatorial immunostimulatory interventions with superior adjuvant activity in patients. Here, we summarize the latest advances in the development of peptide vaccines for cancer therapy.
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  • 文章类型: Review
    现在使用术语“免疫原性细胞死亡”(ICD)来表示功能上独特的凋亡形式,足以使免疫活性宿主产生针对死细胞相关抗原的适应性免疫反应。当用作独立的治疗干预措施时,几种药物被认为具有激发ICD的能力。这些包括临床上常规使用的各种化疗药物(例如,阿霉素,表柔比星,伊达比星,米托蒽醌,博来霉素,硼替佐米,环磷酰胺和奥沙利铂)以及一些仍在临床前或临床开发中的抗癌剂(例如,埃坡霉素家族的一些微管抑制剂)。此外,一些药物能够将细胞死亡的非免疫原性实例转化为真正的ICD,因此可以在组合方案中用作化疗佐剂。强心苷就是这种情况,比如地高辛和洋地黄毒苷,和唑来膦酸.这里,我们讨论了基于ICD诱导剂的抗癌化疗的最新进展。
    The term \"immunogenic cell death\" (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers.
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